Construction and validation of prognostic scoring models to risk stratify patients with acquired immune deficiency syndrome-related diffuse large B cell lymphoma.

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.

Gastroprotective mechanism of modified lvdou gancao decoction on ethanol-induced gastric lesions in mice: Involvement of Nrf-2/HO-1/NF-κB signaling pathway.

Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine formula, has been put into clinical use to treat the diseases of the digestive system for a long run, showing great faculty in gastric protection and anti-inflammatory, whereas its protective mechanisms have not been determined. The current study puts the focus on the protective effect and its possible mechanisms of MLG on ethanol-induced gastric lesions in mice. In addition to various gastric lesion parameters and histopathology analysis, the activities of a list of relevant indicators in gastric mucosa were explored including ALDH, ADH, MDA, T-SOD, GSH-Px, and MPO, and the mechanisms were clarified using RT-qPCR, ELISA Western Blot and immunofluorescence staining. The results showed that MLG treatment induced significant increment of ADH, ALDH, T-SOD, GSH-Px, NO, PGE2 and SS activities in gastric tissues, while MPO, MDA, TNF-α and IL-1ß levels were on the decline, both in a dose-dependent manner. In contrast to the model group, the mRNA expression of Nrf-2 and HO-1 in the MLG treated groups showed an upward trend while the NF-κB, TNFα, IL-1ß and COX2 in the MLG treated groups had a downward trend simultaneously. Furthermore, the protein levels of p65, p-p65, IκBα, p-IκBα, iNOS, COX2 and p38 were inhibited, while Nrf2, HO-1, SOD1, SOD2 and eNOS were ramped up in MLG treatment groups. Immunofluorescence intensities of Nrf2 and HO-1 in the MLG treated groups were considerably enhanced, with p65 and IκBα diminished simultaneously, exhibiting similar trends to that of qPCR and western blot. To sum up, MLG could significantly ameliorate ethanol-induced gastric mucosal lesions in mice, which might be put down to the activation of alcohol metabolizing enzymes, attenuation of the oxidative damage and inflammatory response to maintain the gastric mucosa. The gastroprotective effect of MLG might be achieved through the diminution of damage factors and the enhancement of defensive factors involving NF-κB/Nrf2/HO-1 signaling pathway. We further confirmed that MLG has strong potential in preventing and treating ethanol-induced gastric lesions.

The protective effects and mechanisms of modified Lvdou Gancao decoction on acute alcohol intoxication in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. MATERIALS AND METHODS: AAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. RESULTS: MLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1ß and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Taken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.

Dual therapy with lopinavir/ritonavir plus lamivudine could be a viable alternative for antiretroviral-therapy-naive adults with HIV-1 infection regardless of HIV viral load or subgenotype in resource-limited settings: A randomised, open-label and non-inferiority study from China.

BACKGROUNDS: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-naïve HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). METHODS: 198 were randomised to DT (n = 100) or TT (n = 98). RESULTS: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. CONCLUSION: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.